new discoveries for a healthy future

Loneliness and Health: Effects on the Immune System

We all know that social connectedness positively affects quality of life and well-being. However, not everyone is aware of how profound these effects are. Being socially connected is not only influential for psychological and emotional well-being, but it also has a significant and positive influence on physical well-being. On the other hand, social isolation — one of the invisible epidemics — is linked to an increased risk for chronic diseases and early mortality. Mother Theresa once said: “The biggest disease today is not leprosy or cancer or tuberculosis, but rather the feeling of being unwanted, uncared for and deserted by everybody.”

Notice how the previous quote subtly emphasizes “loneliness” — the feeling of — as compared to “social isolation”. Social isolation is the lack of social interaction, contact, or communication with other people. Those who socially isolate have an absence of relationships with family and friends, or other forms of social networks. Social isolation may be expressed through physical separation with others, social barriers, or psychological mechanisms. Loneliness, as explained by John Cacioppo, has a lot in common with pain, hunger, and thirst, and is a subjective emotional state — it is the perception of social isolation — “You can feel isolated in a crowd. You can also choose to be alone and feel blissful solitude. When people feel others around them are threats rather than sources of cooperation and compassion, they feel socially isolated, lonely.”

Results from a recent meta-analysis, which analyzed data collected from 70 independent published health studies and more than 3.4 million people from 1980 to 2014, show that the influence of both objective and subjective social isolation on risk for mortality is even higher than well-established risk factors for mortality, as for example smoking and obesity. Julianne Holt-Lunstad, lead author of the study, told the New York Times: “The key point that I hope others will get from this is the recognition that this is an important public health issue. Social isolation significantly predicts risk for premature mortality comparable to other well established risk factors. Thus, we need to take our social relationships as seriously for our health as we do these other factors.”

Loneliness is a complex trait, likely influenced by variations within multiple genes — especially genes related to neurotransmitters and the immune system — and their interaction with numerous behavioral and environmental factors. Such factors, as for example low social support, may have a more pronounced effect and lead to higher levels of loneliness if individuals carry the sensitive variant of these genes.

Not surprisingly, then, results from a study published a few days ago by an interdisciplinary team of researchers (November 23, 2015) in the scientific journal Proceedings of the National Academy of Sciences show that loneliness triggers cellular changes caused by fight-or-flight stress responses that increase the chances of getting ill by affecting the immune system. The “danger signals” activated in the brain by feelings of social isolation and loneliness affect the production of white blood cells (leukocytes), the major component of the immune system. For the study, an interdisciplinary group of researchers examined loneliness in both humans and rhesus macaques, a highly social primate species.

Previous research from the same team had identified a link between loneliness and a phenomenon called “conserved transcriptional response to adversity” or CTRA. This response is characterized by an increased expression of genes involved in inflammation, and a decreased expression of genes involved in antiviral responses. In other words, loneliness up-regulates potentially detrimental inflammatory responses, and down-regulates beneficial, protective immune responses.

For the current study, researchers examined gene expression in leukocytes of humans and macaques. Their findings show CTRA effects, and suggest that increased activity of the sympathetic nervous system, which is responsible for the “fight or flight” response, may overstimulate development of monocytes — inflammatory leukocytes — in the bone marrow. At the same time, there is decreased production of the antiviral proteins Type I and II interferons — such decrease may reduce the body’s ability to fight infections. Reduction of the body’s ability to fight infections is confirmed by the impaired response to infection by simian immunodeficiency virus (SIV) observed in macaques, which allowed SIV to grow faster in both macaque blood and brain. SIV is the macaque equivalent of the human immunodeficiency virus (HIV).

The study results also suggest that leukocyte gene expression and loneliness have a reciprocal relationship — each can help propagate the other over time. These results were specific to loneliness and could not be explained by depression, stress or social support.

18 comments

This study sheds some light on how the immune system may not work alone as an isolated system. There is quite a bit of scientific research linking some of the symptoms associated with major depressive disorder. These symptoms include increased feelings of loneness and hopelessness as well as a variety of physical symptoms such as chronic pain and fatigue. It is commonly accepted that loneliness and depression can go hand in hand. Some studies have even linked the inflammatory response of the immune system as a cause of major depressive disorder. It is thought that depression is caused by a chronic, low grade inflammatory response and a heightened level of pro inflammatory cytokines, increased CD4+ and CD8+ T cells, and activated T cells. This chronic inflammation is likely linked to a reduction in 5HT production, thus affecting serotonin production and leading to major depressive disorders. In the case of loneliness affecting the immune system, it’s been discussed before – the body is not made to withstand long-term stress. So it would be expected that the Increased inflammation and associate inflammatory molecules is going to have an impact on how the body functions and how body systems work together.

I suppose I found this article a bit difficult for me to understand because I am having a hard to differentiating between “loneliness” and “social isolation.” The loneliness the article is describing appears to the type caused by feelings of depression and/or social anxiety. However, what if a person is not very social at all and feels happier being a bit more reclusive? I, personally, am a very private person and feel very happy in “blissful solitude,” as the article describes it. My social interactions with others are limited outside of work and school and that is exactly how I like it. It seems to me that the unfavorable immune response derived from the loneliness described in the article comes more from stressful feelings of social anxiety and a feeling on not belonging rather than having a personality prone to not socializing.

Various studies have pointed out to the effect of social stress on the immune system. Stress disturbs the physiological homoeostasis by creating imbalances in the hormones, neurotransmitters and cytokine levels, which result in altered endocrine, nervous and immune functions.
It has been known for quite some time now that stress can suppress the immune responses by suppressing the development of natural killer cells (innate immunity), and suppressing the specific T and B lymphocyte functions (adaptive immunity) that leads to unexpected inflammatory responses. Various studies in mice and humans have shown that psychological stress and the stress-associated immune modulation impact the pathophysiology of a herpes infections, that is, it causes the reactivation of latent herpes simplex virus-1, Epstein–Barr virus and varicella zoster virus.

Source:
Padgett DA, Sheridan JF, Dorne J, Berntson GG, Candelora J, Glaser R. Social stress and the reactivation of latent herpes simplex virus type 1. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(12):7231-7235.

Loneliness not only makes us vulnerable to certain viruses but also leads to increased blood pressure that may lead to heart attacks or stroke. On analyzing blood samples from heart patients, researchers found elevated levels of inflammatory cytokines interleukin-6 (IL-6) and intercellular adhesion molecule 1 (ICAM-1) in the blood, which could be attributed to the increased levels of CTRA gene expression. The presence of these proteins was also linked to the reactivation of latent Epstein-Barr virus(EBV) reactivation. The patients who had a heart attack had highest levels of ICAM-1 and dUTPase protein (an EBV protein). Hence, the viral reactivation might be a link between the stress and the heart disease.

I would assume the function of nuclear binding steroids such as cortisol are a key cause in the observed decreases in cytokine and adhesion molecules. Steroids such as cortisol have the capacity to bind directly to nuclear DNA and effect changes, some which may persist epigenetically in gene expression. Cytokene production appears to be one of the areas most affected. From there, a down regulation of cytokenes such as Interferon Gama themselves may carry out the other observed effects such as a reduction in ICAM expression.

Stress and depression are major psychological disorders which can almost affect every part of the homeostatic system. One can observe a major impact in the CNS and hormone production, both of which play an important in various physiological functions. Glucocorticoids and catecholamine are hormones which gets altered during stress and shows a major impact in the immune system. They inhibit IL-12, TNF-α and INF-γ and stimulate the production of IL-10, IL-4 and TGF-β. Similarly stress hormones induces inflammation through IL-1, IL-6, and IL-8and IL-18. Thus causing Th1/Th2 cytokine imbalance. These results in autoimmunity, chronic infections and atherosclerosis. The stress hormone induced inhibition or stimulation of innate and adaptive immunity cytokines affects disease susceptibility and causes various immune related diseases.
References:
1. Calcagni E, Elenkov I. Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases.Ann N Y Acad Sci. 2006 Jun; 1069:62-76.
2. Elenkov IJ, Chrousos GP. Stress Hormones, Th1/Th2 patterns, Pro/Anti-inflammatory Cytokines and Susceptibility to Disease.Trends Endocrinol Metab. 1999 Nov; 10(9):359-368.

It’s very interesting to consider that emotions such as loneliness can have such a profound effect on the immune system. However, I found the article’s primary assumption – that the effects of loneliness are negative – to be biased. The negative aspects of loneliness (for example, increased expression of genes involved in inflammation, and down-regulation of antiviral genes), may not have been negative for our ancestors, who lived in much more dangerous times than modern society. There’s likely an evolutionary explanation for why loneliness has such a dramatic impact on the immune system.

Lonelier people are likely to have less social contact with others, potentially reducing their rate of infection from contagious diseases. Thus, down-regulated antiviral genes may not be entirely detrimental, and may instead conserve energy for more important functions.

CTRA increases the activity of the sympathetic nervous system (fight-or-flight response), and also stimulates monocyte activity. These are possibly evolutionary adaptions that would benefit people who have little human contact with others. A heightened fight-or-flight response could have helped our primitive ancestors, and would have been especially critical to an isolated individual without assistance from his/her tribe. Stimulated monocyte activity would boost an individual’s innate immune response, which may be important for an isolated person, as he/she would have no one else to care for him or her.

Certainly, the article raises an interesting point. For me, the take home message is that nearly all aspects of our life have an effect on the others, and connections can be drawn where we wouldn’t otherwise think they exist. It’s incredibly fascinating to discover how some facets of our lives are interconnected, and we will only learn more about ourselves in the future.

I agree with you – social isolation does eliminate the risk of exposure to infectious disease. However another effect of this social isolation would be that lonely people might be less likely to seek medical care. In particular, elderly people are more likely suffer from a variety of medical issues due to reduced social interactions and perceived loneliness. Problems sleeping, increased blood pressure, reduced immunological responses, and deficits to cognition are just some of the issues commonly seen in elderly people who are characterized as lonely. When diagnosing and treating medical conditions, the whole person must be considered, not just the immediate problem.

I agree with Beth on considering the whole person when diagnosing and treating medical conditions. I often find my self in “social isolation” when I am very busy or working hard to complete an assignment or prepare for an exam. It seems like there is something about stress, lack of sleep, and isolation that leads to immunological disorders such as chronic inflammation. In addition, I think loneliness and the symptoms that it can cause could eventually result in depression. One thing I’ve learned from all the people I’ve met is that you never know what someone is going through and most people are going through something they consider to be stressful.

With the advent of social media, how do the technological superpowers such as Twitter, Facebook and Instagram affect these metrics of loneliness? As the world becomes increasingly interconnected via the Internet, the web of an individual’s social life continues to rapidly expand and grow. Studies have shown that even brief chat sessions with anonymous strangers have positive impacts on participants, notably a decrease in depression and loneliness. As the world continues to become even more interconnected, will we see that social media can diminish, or even eliminate the concept of loneliness entirely?

Zachary, that is a great finding and I agree social media can be used to help people communicate and fulfill the emotional need for human interaction to prevent depression. But, social media should not be used as substitution for human interaction. According to the CDC in 2011, 1 out of 10 Americans suffer from depression and ages 18-24 are more likely to suffer from depression (2), these are the age groups that use social media the most. In a 2015 study with 736 college students the use of Facebook caused envy related depression (1). Staying isolated in the house with only having contact with people through face chat and social media my help prevent exposure to outside pathogens but puts you at risk for depression. Studies have shown depression is linked to immune suppression. In a study with elderly patients that suffer from depression reduced immune response to varicella zoster vaccination was observed (3). Untreated depression in elderly patients increases the risk for shingles outbreaks (3).

To quote the findings of the Pew Research Center, a Washington think tank:

“We looked at how much total support, emotional support, companionship, and instrumental aid adults receive. On a scale of 100, the average American scored 75/100 on a scale of total support, 75/100 on emotional support (such as receiving advice), 76/100 in companionship (such as having people to spend time with), and 75/100 in instrumental aid (such as having someone to help if they are sick in bed).

Internet users in general score 3 points higher in total support, 6 points higher in companionship, and 4 points higher in instrumental support. A Facebook user who uses the site multiple times per day tends to score an additional 5 points higher in total support, 5 points higher in emotional support, and 5 points higher in companionship, than internet users of similar demographic characteristics. For Facebook users, the additional boost is equivalent to about half the total support that the average American receives as a result of being married or cohabitating with a partner.”

This conflicting evidence suggests that the mosiac impact of how social media impacts the social lives of an individual is multifocal, as this evidence would suggest that social media would positively impact feelings of isolation, leading to no negative impact to immunological function. While I am not suggesting social media replace the entirety of face to face human interaction, I wouldn’t rule it out as a possibility in the future, requiring us to accept tech as an innovation to the human experience.

I agree with you, Zach, that there is a lot of conflicting evidence about the effect of social media on the psychological well-being of its users. However, Dessica brings up good points about social media and how it cannot be substitutes for genuine interactions. Social media is designed to make you ‘feel’ like you are connected to a whole world because you assume that the attention given to you by having a comment or picture ‘liked’ equals the amount of understanding and empathy that a person is capable of feeling for you at the moment.

If you recall a few weeks ago about the Instagram model who broke the silence of what everyone thought was a perfect life by taking down most of her pictures and starting to proclaim that “social media is a lie” [1]. Even though for years she thought that all those people commenting on her pictures and following her work were people she could at some point rely on, she found that at the end of the day they were just comments on a screen and not an actual support system. She says that she became “addicted to what others thought of me, simply because it was so readily available”.

The fact of the matter is that replacing so much of normal human interaction by using social media we are losing vital social skills that we learn when we are just children. We forget that we have to actually listen to what people have to say and if they come to us for a problem that we should do our best to offer advice. Social media helps a lot of people forget that behind every screen there is a human being (I mean, look at the comments section of any YouTube video and you’ll see what I’m talking about) and that therefore you can say whatever pops into your head. While I am a big fan of these social media outlets because they help me stay connected to my family back home, I can’t say that they have boosted my support system or that they are the way forward in social interaction. To me there is nothing that can replace a good face-to-face conversation and a hug when I’m not feeling myself, and all the ‘likes’ and ‘favorites’ in the world fall short to the simplicity of spending an afternoon with a friend.

This is an interesting link between loneliness and the functions of the immune system. Sine the immune system is linked to the CNS, it is not hard to believe that loneliness would, in fact, contribute to a weakened immune response. Reading this brought out this humorous idea that “hmmm, maybe the immune system over stimulates the production of monocytes because it recognize “people” as foreign pathogens”. ☺ ☺ Honestly, I feel as though the loneliness is definitely a response of a defect in the brain, which in turn, could be the direct link to the immune system and how it functions. The brain controls everything, so if something is going wrong in the brain, this will essentially attack the body’s normal response. I would love to see more studies on the effects of loneliness on the immune system. Feeling lonely goes hand in hand with feeling depressed or sad. I feel the social realm that we are placed in is what keeps us up to par, health wise and mentally, as well. All types of atypical happenings trigger the immune system; therefore, loneliness as a trigger should not be as surprising.

Very true- the brain controls all- mood, feeling, emotions, hormones, personality, etc. I don’t really agree in that loneliness is a defect in the brain. I think people become lonely because of experiences in their life. Either they have had a traumatic experience where they lost someone close to them, they have anxiety or social problems, or physical qualities that make them feel insecure in public. Some people indeed are born with defects or brain abnormalities that result in social disorders, but for those that are healthy/normal, loneliness and social problems usually arise from experiences growing up in life. Also, someone can be lonely but not have any defect in their brain. Everyone experiences times of loneliness, but it is depression and true social isolation that leads to the immune dysfunction.

If we do treat loneliness as a defect in the brain, then really the only solutions would be medication to treat the problem in the brain, or surgery. The former is the most plausible solution to treating loneliness/depression. However, medicines have a lot of side effects too (antidepressants can cause someone to feel suicidal), so there must be careful consideration when treating someone’s (brain) with depression.

Reading this blog post, many thoughts came to mind. The one that I milled around with for the longest was the fact that we, as part of the digital age, have managed to somehow isolate ourselves from the world even though connection is at our fingertips. I honestly think that is the very reason we have taken ordinary human connections for granted. I have caught myself on more than one occasion ignoring phone calls and then texting the person because I have found the action of talking on the phone so time consuming that I don’t want to deal with it. We want to be able to multitask connecting with another person while we deal with other trivial matters. We are all about convenience and end-game. Is this affecting our health in more ways than one?

A few sources have already talked about the impact of social media in the lives of Millenials, and all have pointed that this ability to be able to communicate evry thought, feeling and whim at a moment’s notice is actually making us sadder [1,2] because our minds automatically begin comparing our lives, our accomplishment and our goals to the lives and goals of others; and sometimes, we perceive other people as knowing exactly what they are doing with their lives while we are seemingly stuck in a rut. The study done by Cole, et al (referenced in the original blog post) found a connection between these feelings of sadness and isolation with responses being made by our immune system.

The news does not come as a complete surprise to me, because when I think about someone who is either feeling isolated or is battling through a bout of depression, I think about a person who does is not taking the necessary precautions to stay in good health, pale and always battling through some sort of bug. And while I know that a lot of people who battle depression also try to put up a front to seem OK to their friends and family, it has also been noted that they often begin suffering from autoimmune diseases [3]. While the original Cole study claims that their results cannot be explained by depression or stress and is attributed mainly to loneliness, it gives us, as a scientific community, a new persepective of what we can consider physical diseases. The loneliness and isolation may be a frame of mind, but this situation is certainly pressuring the immune system to think that something is wrong and to act erratically. I would love to see more research unifying the idea of declining psychological well-being and physical decline, so that both might problems might find the treatments avenues they deserve.

With the social problems in today’s society, this article really sheds light on the importance of being in a social circle, feeling connected, interacting with other people, and having friends/family. I’ve always heard that happiness and health comes with friends. As Zach mention social media can help for social interaction, and I believe that is a great resource. Some people have real mental problems because of whatever reason (weight, anxiety, abuse, etc.) and they may not be able to leave or be comfortable leaving their house to interact with others. Social media and even interacting with strangers through video games seem to help them not be so lonely. Just having them look forward to talking with people online or through a game could help them. Yes, it’s not the same as in-person human interaction, but it will at least help these people suffering from loneliness. The main problem with loneliness is being depressed, leading to immune suppression. You can be lonely, but not depressed, in my belief. I think the bigger problem with loneliness is not decreased immune function, but suicide or anger issues that can lead to killing of others, from being lonely, and depressed.

Also, if someone is more lonely, they will most likely spend more time inside, thus not getting any/enough sunlight, therefore may have low vitamin D levels. This is also going to influence the immune system. Low vitamin D levels could cause autoimmune diseases, such as Multiple Sclerosis. I think that is another major issue to discuss as well. Also, those that are lonely will most likely have a poor diet, gain weight, have obesity, cardiovascular disease, diabetes, etc. So, I don’t believe that being lonely and depressed will really impact their immune system. It seems like it will from the studies in the article, but what really will effect/kill these people are the diseases from their eating habits and sedentary lifestyle.

The results of this study don’t really surprise me considering most animals do rely on pack interactions. We, as humans, are no different. Since we are emotional animals, it makes sense that the perceived loneliness and social isolation would induce systemic effects given how sensitive our endocrine and nervous systems are to stress whether emotional or physical. In Lisa Jaremka’s 2013 article “Loneliness promotes inflammation during acute stress” results from two different studies showed that lonelier participants showed elevated pro inflammatory cytokine production than their counterparts when exposed to stress. This connection between social isolation, loneliness and the immune system makes me wonder if people with social anxiety disorders or autism spectrum disorders have immune dysfunctions. Could be an interesting study to further connect emotional response to physical effects.